Long-term outcomes of prostate intensity-modulated radiation therapy incorporating a simultaneous intra-prostatic MRI-directed boost.

Purpose/objectives: This retrospective study demonstrates the long-term outcomes of treating prostate cancer using intensity modulated (IMRT) with incorporation of MRI-directed boost. Materials/methods: From February 2009 to February 2013, 78 men received image-guided IMRT delivering 77.4 Gy in 44 fractions with simultaneously integrated boost to 81-83 Gy to an MRI-identified lesion. Patients with intermediate-risk or high-risk prostate cancer were recommended to receive 6 and 24-36 months of adjuvant hormonal therapy, respectively. Results: Median follow-up was 113 months (11-147). There were 18 low-risk, 43 intermediate-risk, and 17 high-risk patients per NCCN risk stratification included in this study. Adjuvant hormonal therapy was utilized in 32 patients (41%). The 10-year biochemical control rate for all patients was 77%. The 10-year biochemical control rates for low-risk, intermediate-risk, and high-risk diseases were 94%, 81%, and 88%, respectively (p = 0.35). The 10-year rates of local control, distant control, and survival were 99%, 88%, and 66%, respectively. Of 25 patients who died, only four (5%) died of prostate cancer. On univariate analysis, T-category and pretreatment PSA level were associated with distant failure rate (p = 0.02). There was no grade =3 genitourinary and gastrointestinal toxicities that persisted at the last follow-up. Conclusions: This study demonstrated the long-term efficacy of using MRI to define an intra-prostatic lesion for SIB to 81-83Gy while treating the entire prostate gland to 77.4 Gy with IMRT. Our study confirms that modern MRI can be used to locally intensify dose to prostate tumors providing high long-term disease control while maintaining favorable long-term toxicity.

Urinary Pubic Symphysis Fistula Leads to Histopathologic Osteomyelitis in Prostate Cancer Survivors.

OBJECTIVE: To assess the histologic findings in the pubic bone resected during extirpative surgery for urinary pubic symphysis fistula (UPF). The concurrent presence of osteomyelitis and the need for bone resection at time of extirpative surgery for UPF has been debated. We hypothesized that UPF results in histopathologically confirmed osteomyelitis, underscoring the importance of bone resection at the time of surgery. METHODS: An IRB-approved retrospective review of all patients undergoing surgery for UPF from 2012 to 2019 was performed. Demographic data were recorded. A single pathologist performed histopathologic examination of bone tissue in each case. Logistic regression and Fisher exact test were used to assess association of osteomyelitis with clinical factors. RESULTS: We identified 36 patients who underwent major extirpative surgery for UPF with bone pathology available for review. Bone histopathology findings confirmed presence of osteomyelitis in the majority (n = 32, 88.9%). This was characterized as chronic osteomyelitis in 15 (41.7%), acute osteomyelitis only in 1 (2.8%) and combined chronic, and acute osteomyelitis in 16 (44.4%). Osteonecrosis was seen in 11 cases (33.6%). There was no correlation between presence of osteomyelitis and age, timing from radiotherapy to diagnosis of UPF, type of radiotherapy, or history of endoscopic bladder outlet procedures. CONCLUSION: Osteomyelitis is present on histology of the pubic bone resected during surgery for UPF in the majority of cases (88.9%). Osteonecrosis is also common. These findings underscore the critical importance of pubic bone resection at time of UPF surgery to adequately treat the diseased bone.

A Rare Case of a Cervical Thymic Cyst Presenting in Adulthood.

The cervical thymic cyst (CTC) is a rare, benign neck mass that most commonly presents in the pediatric population. These entities can occur anywhere along the normal path of descent of the thymus from the mandible to the sternal notch, and extension into the mediastinum has been observed. The presentation of these masses is often characterized by a painless, enlarging neck mass in a child during the first decade of life. Although most patients are asymptomatic, abutment of the cyst against local structures has led to a variety of presentations including respiratory distress. These rare lesions are noted to have a male predominance and most commonly present on the left side of the neck. We present the rare case of a 19-year-old male who presented with a left-sided painless, cystic neck mass. He underwent a computed tomography scan of the neck which showed a large cystic mass in the left neck deep to the sternocleidomastoid muscle. Preoperatively, the diagnosis of an infected third branchial cyst was favored. The lesion was completely excised in the operating room. Final pathology was consistent with a CTC. The CTC is an uncommon benign process that often presents as an asymptomatic cystic neck mass. Knowledge of the clinical presentation, diagnostic process, and treatment of these rare lesions is essential for the Otolaryngologist.

Nonalcoholic Steatohepatitis: Histopathology Basics Within a Broader Context.

Nonalcoholic fatty liver disease (NAFLD) is a major health concern and the prevalence continues to increase in many industrialized and developing countries around the world. NAFLD affects adults and children. NAFLD-related cirrhosis is expected to become the top indication for liver transplantation in the near future, and the incidence of NAFLD-related hepatocellular carcinoma is also increasing. Nonalcoholic steatohepatitis is the more severe form of NAFLD. The pathogenesis of NALFD/nonalcoholic steatohepatitis is complex and new concepts continue to evolve. The diagnosis and categorization of nonalcoholic steatohepatitis currently rests on hepatopathologists. Accurate morphologic interpretation is important for therapeutic, prognostic, and investigational purposes.

A Prospective Trial of Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Integrated Boost for Prostate Cancer: Long-term Outcomes Compared With Standard Image Guided IMRT.

PURPOSE: This report describes the long-term outcomes of a prospective trial of intensity modulated radiation therapy (IMRT), integrating a 111In capromab pendetide (ProstaScint) scan-directed simultaneous integrated boost (SIB) for localized prostate cancer. METHODS AND MATERIALS: Seventy-one patients with T1N0M0 to T4N0M0 prostate cancer were enrolled, and their ProstaScint and pelvic computed tomography scans were coregistered for treatment planning. The entire prostate received 75.6 Gy in 42 fractions with IMRT, whereas regions of increased uptake on ProstaScint scans received 82 Gy as an SIB. Patients with intermediate- and high-risk disease also received 6 months and 12 months of adjuvant hormonal therapy, respectively. RESULTS: The study enrolled 31 low-, 30 intermediate-, and 10 high-risk patients. The median follow-up was 120 months (range, 24-150 months). The 10-year biochemical control rates were 85% for the entire cohort and 84%, 84%, and 90% for patients with low-, intermediate-, and high-risk disease, respectively. The 10-year survival rate of the entire cohort was 69%. Pretreatment prostate-specific antigen level >10 ng/mL and boost volume of >10% of the prostate volume were significantly associated with poorer biochemical control and survival. The outcomes were compared with those of a cohort of 302 patients treated similarly but without the SIB and followed up for a median of 91 months (range, 6-138 months). The 5- and 10-year biochemical control rates were 86% and 61%, respectively, in patients without the SIB compared with 94% and 85%, respectively, in patients in this trial who received the SIB (P=.02). The cohort that received an SIB did not have increased toxicity. CONCLUSIONS: The described IMRT strategy, integrating multiple imaging modalities to administer 75.6 Gy to the entire prostate with a boost dose of 82 Gy, was feasible. The addition of the SIB was associated with greater biochemical control but not toxicity. Modern imaging technology can be used to locally intensify the dose to tumors and spare normal tissues, producing very favorable long-term biochemical disease control.

Statins and Metformin Use Is Associated with Lower PSA Levels in Prostate Cancer Patients Presenting for Radiation Therapy.

BACKGROUND: A possible association between the level of prostate specific antigen (PSA) and the use of some commonly prescribed medications has been reported in recent studies. Most of these studies were carried out in general populations of men who were screened for prostate cancer using the PSA test. We reported on the association between the initial PSA level and the use of statins, metformin and alpha-blockers in patients who were diagnosed with prostate cancer and presented for radiation therapy. METHODS: Three hundred and eighty one patients treated between the years of 2000-2005 and 2009-2012 were included in this retrospective study. The information about statin, metformin and alpha-blockers use was recorded immediately prior to treatment. Differences in PSA levels prior to treatment by medication status were estimated using univa-riate and multivariate linear regression on log PSA values. RESULTS: Compared with men who were not on these medications, the PSA level at presentation was 20% lower for statin users (p = 0.002) and 33% lower for metformin users (p = 0.004). We did not observe statistically significant associations between the use of statins or metformin and cancer stage, National Comprehensive Cancer Network (NCCN) risk score, or therapy outcome. A statistically significant association between the NCCN risk score and the use of alpha-blockers was observed (p = 0.002). CONCLUSIONS: We found that statins and metformin were associated with lower PSA levels in prostate cancer patients to an extent that could influence management decisions. We found no statistically significant associations between the use of these medications and treatment outcomes.

Patient Specific Characteristics Are an Important Factor That Determines the Risk of Acute Grade ≥ 2 Rectal Toxicity in Patients Treated for Prostate Cancer with IMRT and Daily Image Guidance Based on Implanted Gold Markers.

AIM: To model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics. METHODS: A database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models. RESULTS: Sixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1-0.16), slope m=0.09 (0.08-0.11), and threshold dose TD50=56.8 (53.7-59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the remainder (p=0.01). CONCLUSIONS: Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.

Langerhan's Cell Sarcoma: Two Case Reports.

Langerhan's cell sarcoma (LCS) is a rare neoplasm with a poor prognosis. To our knowledge, only sixty-six cases have been published. We discuss two patients who presented very differently with LCS, as well as a recently published review of all sixty-six cases. Our first case had a complicated history of metastatic, high-grade myxofibrosarcomas and presented with a single skin lesion of LCS which was treated with resection to a positive margin and adjuvant radiotherapy. The LCS recurred locoregionally and was again resected. The patient is alive two years after initial diagnosis. The second case presented with bone marrow and splenic involvement, leukocytosis, and thrombocytopenia. This patient had an excellent response to etoposide, prednisone, oncovorin, cyclophosphamide, and adriamycin, with normalization of the complete blood count, negative bone marrow biopsy at follow up, and splenectomy without viable neoplasm. This patient is alive without signs of disease at 16 months after initial diagnosis.

Primary pulmonary classical Hodgkin lymphoma: a case report.

Primary pulmonary Hodgkin lymphoma (PPHL) is a rare entity. Most reported cases occurred before the availability of PET scan for accurate staging of the disease. We report a case of PPHL for which PET/CT scan was used and surgery was performed to confirm the diagnosis. A review of cases of PPHL since 1990 suggests that adjuvant chemotherapy and/or radiation therapy after surgical resection of the lung lesions achieve better disease control than surgical resection alone.

Early Outcome of Prostate Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Intra-Prostatic MRI Directed Boost.

This study assessed the feasibility and outcomes of treating prostate cancer with intensity modulated radiotherapy (IMRT) incorporating a Magnetic Resonance Imaging (MRI) directed boost. Seventy-eight men received IMRT for localized prostate cancer. The entire prostate received 77.4Gy in 43 fractions and simultaneous intra-prostatic boosts (SIB) of 83Gy were administered to increase the dose to the MRI identified malignancy. In 16 (21%) patients, the MRI didn't detect a neoplasm and these patients received an SIB of 81Gy to the posterior prostate. Androgen Deprivation Therapy (ADT) was also administered to 32 (41%) patients. The 3-year rates of biochemical control, local control, distant control, and survival were 92%, 98%, 95%, and 95% respectively. While grade 1-2 toxicities were common, there were only 2 patients who suffered grade 3 toxicity. These patients developed strictures which were dilated resulting in improvement in symptoms such that both had grade 1-2 toxicity at last follow up examination. The results of this program of IMRT incorporating a MRI directed intra-prostatic boost suggest this technique is feasible and well tolerated. This technique appears to shift the therapeutic index favorably by boosting the malignancy to the highest dose without increasing the doses administered to the bladder and rectum.